The small intestine has the dual function of being an absorptive organ as well as a barrier to permeation of toxic compounds and macromolecules. Systemic problems result if either of these functions is disrupted. Increased permeability of the intestinal mucosal barrier correlates with a number of common medical disorders, while decreased permeability appears as a fundamental cause of malnutrition, malabsorption, and failure to thrive. Changes in gut permeability are seen in disorders such as inflammatory bowel disease, Crohn's disease, inflammatory joint disease, food allergy, celiac disease, rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, chronic dermatological conditions, schizophrenia, irritable bowel syndrome, allergic disorders, type 1 and type 2 diabetes mellitus, obesity, cancer, environmental enteropathy, autism spectrum disorders and Parkinson's disease. Measurement and manipulation of intestinal permeability is of interest in chemotherapy, disease and treatment monitoring and also drug safety.
Current assessment of small intestinal permeability typically involves oral ingestion of sugar markers such as lactulose and mannitol, followed by collection of urine for 6 hours. The amount of lactulose and mannitol excreted into urine is then measured using HPLC separation coupled to a detector such as a mass spectrometer or evaporative light scatter detector. Alternatively, NADPH-coupled enzyme assays are used. Both methods require considerable time and cost. Currently available technology does not allow rapid, direct quantification of the sugar markers because neither lactulose nor mannitol has intrinsic absorbance or fluorescence.
Thus, a need exists to simplify the measurement and increase throughput of intestinal permeability while lowering the cost per sample.